3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion
Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix sti...
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MDPI AG
2023-09-01
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| Series: | Biomimetics |
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| Online Access: | https://www.mdpi.com/2313-7673/8/5/421 |
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| author | Meitham Amereh Amir Seyfoori Briana Dallinger Mostafa Azimzadeh Evan Stefanek Mohsen Akbari |
| author_facet | Meitham Amereh Amir Seyfoori Briana Dallinger Mostafa Azimzadeh Evan Stefanek Mohsen Akbari |
| author_sort | Meitham Amereh |
| collection | DOAJ |
| description | Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model’s predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion. |
| first_indexed | 2024-03-10T23:00:55Z |
| format | Article |
| id | doaj.art-f2da28c7bba547edb1b26ffaf7c8c9e2 |
| institution | Directory Open Access Journal |
| issn | 2313-7673 |
| language | English |
| last_indexed | 2024-03-10T23:00:55Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomimetics |
| spelling | doaj.art-f2da28c7bba547edb1b26ffaf7c8c9e22023-11-19T09:44:16ZengMDPI AGBiomimetics2313-76732023-09-018542110.3390/biomimetics80504213D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor InvasionMeitham Amereh0Amir Seyfoori1Briana Dallinger2Mostafa Azimzadeh3Evan Stefanek4Mohsen Akbari5Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaLaboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaLaboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, CanadaGlioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model’s predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.https://www.mdpi.com/2313-7673/8/5/4213D-printingtumor-on-a-chipglioblastomain silico model |
| spellingShingle | Meitham Amereh Amir Seyfoori Briana Dallinger Mostafa Azimzadeh Evan Stefanek Mohsen Akbari 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion Biomimetics 3D-printing tumor-on-a-chip glioblastoma in silico model |
| title | 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion |
| title_full | 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion |
| title_fullStr | 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion |
| title_full_unstemmed | 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion |
| title_short | 3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion |
| title_sort | 3d printed tumor on a chip model for investigating the effect of matrix stiffness on glioblastoma tumor invasion |
| topic | 3D-printing tumor-on-a-chip glioblastoma in silico model |
| url | https://www.mdpi.com/2313-7673/8/5/421 |
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